American Journal of Hypertension · 1996 · 599 citations · 36 references
MedicineCardiologyPharmacologyCardiovascular PharmacotherapyClinical CardiologyPreventive CardiologyBlood Pressure ManagementCardiovascular DiseaseCardiovascular Disease PreventionCoronary Artery DiseaseHypertension PreventionLipid-lowering TherapyAlpha-adrenergic Blocker TherapyAntihypertensive Drug TherapyCardiovascular Disease IncidenceCardiovascular Disease MortalityDouble-blind TrialsLdl Cholesterol LoweringLipid-lowering Drug EfficacyLow-density Lipoprotein Cholesterol Lowering
Newer antihypertensive agents are more expensive than diuretics, and it is unclear whether they are as effective in preventing coronary heart disease, while lowering LDL cholesterol may reduce cardiovascular disease and mortality in older adults. ALLHAT was designed to test whether diuretics are as effective as calcium antagonists, ACE inhibitors, or α‑adrenergic blockers in preventing CHD and MI, and whether pravastatin lowers LDL to reduce all‑cause mortality. The study randomized 40,000 high‑risk hypertensive patients to diuretic or alternative antihypertensives in a double‑blind design, and a subset of 20,000 hypercholesterolemic patients to pravastatin or usual care in an open‑label arm, with 6‑year follow‑up and LDL thresholds of 120–189 mg/dL. Am J Hypertens 1996;9:342–360.
Are newer types of antihypertensive agents, which are currently more costly to purchase on average, as good orbetter than diuretics in reducing coronary heart disease incidence and progression? Will lowering LDL cholesterol in moderately hypercholesterolemic older individuals reduce the incidence of cardiovascular disease and total mortality? These important medical practice and public health questions are to be addressed by the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind trial in 40,000 high-risk hypertensive patients. ALLHAT is designed to determine whether the combined incidence of fa tal coronary he art disease (CHD) and nonfatal myocardial infarction differs between persons randomized to diuretic (chlorthalidone) treatment and each of three alternative treatments—a calcium antagonist (amlodipine), an angiotensin converting enzyme inhibitor (lisinopril), and an α -adrenergic blocker (doxazosin). ALLHAT also contains a randomized, open-label, lipid-lowering trial designed to determine whether lowering LDL cholesterol in 20,000 moderately hypercholesterolemic patients (a subset of the 40,000) with a 3-hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor, pravastatin, will reduce all-cause mortality compared to a control group receiving “usual care.” ALLHAT's main eligibility criteria are: 1) age 55 or older; 2) systolic or diastolic hypertension; and 3) one or more additional risk factors for heart attack (eg, evidence of atherosclerotic disease or type II diabetes). For the lipid-lowering trial, participants must have an LDL cholesterol of 120 to 189 mg/ dL (100 to 129 mg/ dL for those with known CHD) and a triglyceride level below 350 mg/dL. The mean duration of treatment and follow-up is planned to be 6 years. Further features of the rationale, design, objectives, treatment program, and study organization of ALLHAT are described in this article. Am J Hypertens 1996;9:342–360
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